COVID-19 vaccine effectiveness (VE) studies are limited in low- and middle-income countries. A case-control study was conducted among COVID-19 and other pneumonia patients admitted to a hospital in the Philippines during the pre-Omicron and Omicron periods. To elucidate factors associated with in-hospital death, 1782 COVID-19 patients were assessed. To estimate absolute VE for various severe outcomes, 1059 patients were assessed (869 [82.1%] COVID-19 cases; 190 [17.9%] controls). Factors associated with in-hospital death included older age, tuberculosis (adjusted odds ratio [aOR] 2.45 [95% confidence interval {95% CI} 1.69–3.57]), HIV (aOR 3.30 [95% CI 2.03–5.37]), and current smokers (aOR 2.65 [95% CI 1.72–4.10]). Pre-Omicron, the primary series provided high protection within a median of 2 months (hospitalization: 85.4% [95% CI 35.9–96.7%]; oxygen requirement: 91.0% [95% CI 49.4–98.4%]; invasive mechanical ventilation (IMV): 97.0% [95% CI 65.7–99.7%]; death: 96.5% [95% CI 67.1–99.6%]). During Omicron, the primary series provided moderate-high protection within a median of 6–9 months (hospitalization: 70.2% [95% CI 27.0–87.8%]; oxygen requirement: 71.4% [95% CI 29.3–88.4%]; IMV: 72.7% [95% CI −11.6–93.3%]; death: 58.9% [95% CI −82.8–90.8%]). Primary series VE against severe COVID-19 outcomes was consistently high for both pre-Omicron and Omicron in a setting where approximately half of the vaccinees received inactivated vaccines.
